Ethanol perturbs a multitude of cellular functions because of its free access to all cellular compartments. The differential impact of ethanol on various tissue most likely relates to fundamental molecular differences between cells. In order to determine the concentration-dependent and temporal-dependent effect of ethanol on cellular events at the molecular level, we have been working with a well-characterized tumor cell line (AtT-20 cells) of anterior pituitary origin, which contains multiple membrane receptors and secretes several stress hormones. Our approach is to understand the effect of ethanol on the sequence of events from membrane-receptor activation to intracellular-messenger systems to physiological responses. Our results suggest that ethanol differentially affects certain cellular events in a dose-and duration-related manner. Ethanol alone lowers basal beta-endorphin secretion and elevates cAMP, which is incongruous, assuming basal secretion is linked to activation of adenylate cyclase and formation of cAMP. In most instances, enhanced cAMP levels in AtT-20 cells results in increased hormone secretion. Ethanol, in addition to stimulating adenylate cyclase activity, may prevent calcium influx or mobilization of calcium from intracellular compartments, which would prevent increased cAMP formation from enhancing hormone release. Enhanced binding of CRF to AtT-20 cells in the presence of ethanol, most likely, explains CRF's ability to override the ethanol induced reduction of basal secretion of beta-endorphin. As a result of enhanced-CRF binding, CRF-induced beta-endorphin secretion in the presence or absence of ethanol is similar.